{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:26:28Z","timestamp":1790724388736,"version":"4.1.0"},"reference-count":23,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870685"],"award-info":[{"award-number":["81870685"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["7172173"],"award-info":[{"award-number":["7172173"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Beijing Municipality","award":["81870685"],"award-info":[{"award-number":["81870685"]}]},{"name":"Natural Science Foundation of Beijing Municipality","award":["7172173"],"award-info":[{"award-number":["7172173"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myopia, one of the most prevalent ocular diseases worldwide, is projected to affect nearly half of the global population by 2050. The main cause of myopia in most patients is axial myopia, which primarily occurs due to the elongation of the eyeball, driven by changes in the extracellular matrix (ECM) of scleral cells. Previous studies have shown that NLRP3, an important inflammatory mediator, plays a critical role in regulating the expression of MMP-2 in the sclera. This, in turn, leads to a decrease in the expression of Collagen-1, a major component of the scleral ECM, triggering the remodeling of the scleral ECM. This study aimed to investigate the effect of MCC950, an inhibitor of NLRP3, on the progression of myopia using a mouse form-deprivation myopia (FDM) model. The FDM mouse model was constructed by subjecting three-week-old C57BL\/6J mice to form-deprivation. The mice were divided into experimental (n = 10\/group; FDM2M, FDM4M, FDM2W, and FDM4W) and control groups (n = 5\/group). The experimental groups were further categorized based on the duration of form deprivation (2 and 4 weeks, labeled as 2 and 4, respectively) and the type of injection received (MCC950 or saline, labeled as M and W, respectively). MCC950 was injected at a concentration of 50 mg\/mL, with a dose of 10 mg per kilogram of body weight. Meanwhile, the saline group received the same volume of saline. Refraction and axial length measurements were performed for each eye. The expression levels of NLRP3, caspase-1, IL-1\u03b2, IL-18, MMP-2, and Collagen-1 in the sclera were assessed using immunohistochemistry and Western blotting. The intraperitoneal injection of MCC950 did not significantly affect refraction or axial length in normal mice (p &gt; 0.05). However, in FDM mice, MCC950 attenuated the elongation of the axial length and resulted in a smaller shift towards myopia compared to the saline group (FDM4M vs. FDM4W, p = 0.03 and p &lt; 0.05, respectively). MCC950 decreased MMP-2 expression (p &lt; 0.05) but increased Collagen-1 expression (p &lt; 0.05) in the experimental eyes when compared to the saline group. Within the MCC950 group, the expression of MMP-2 was increased in the experimental eyes at 4 weeks (p &lt; 0.05), while that of Collagen-1 was decreased (p &lt; 0.05), which is consistent with changes in refractive error. Immunohistochemical analysis yielded similar results (p &lt; 0.05). MCC950 also reduced the expression levels of NLRP3 (p = 0.03), caspase-1 (p &lt; 0.05), IL-1\u03b2 (p &lt; 0.05), and IL-18 (p &lt; 0.05) in the experimental eyes compared to the saline group. Within the MCC950 group, the expression levels of NLRP3 and caspase-1 were comparable between the experimental and control eyes (p &gt; 0.05), whereas IL-18 expression was higher in experimental eyes (p &lt; 0.05). IL-1\u03b2 expression was higher in the experimental eyes only at week 4 (p &lt; 0.05). The intraperitoneal injection of MCC950 can inhibit the progression of myopia in FDM mice, possibly by regulating collagen remodeling in the sclera through the NLRP3-MMP-2 signaling pathway. Therefore, MCC950 holds promise as a potential therapeutic agent for controlling the progression of myopia.<\/jats:p>","DOI":"10.3390\/ijms242115839","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T11:16:27Z","timestamp":1698750987000},"page":"15839","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Intraperitoneal Injection of MCC950 Inhibits the Progression of Myopia in Form-Deprivation Myopic Mice"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8892-5699","authenticated-orcid":false,"given":"Zhengyu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"},{"name":"Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"},{"name":"Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China"},{"name":"Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences, Beijing 100730, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1016\/S0140-6736(12)60272-4","article-title":"Myopia","volume":"379","author":"Morgan","year":"2012","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1097\/OPX.0b013e31819f9bc5","article-title":"Correlation Between Myopia and Major Biometric Parameters of the Eye: A Retrospective Clinical Study","volume":"86","author":"Xie","year":"2009","journal-title":"Optom. Vis. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.exer.2005.08.009","article-title":"The sclera and myopia","volume":"82","author":"Jody","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/978-1-4939-7407-8_13","article-title":"Quantification of Scleral Biomechanics and Collagen Fiber Alignment","volume":"1695","author":"Campbell","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9684","DOI":"10.1167\/iovs.11-7894","article-title":"Quantitative mapping of scleral fiber orientation in normal rat eyes","volume":"52","author":"Girard","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","first-page":"1380","article-title":"Form-deprivation myopia induces activation of scleral matrix metalloproteinase-2 in tree shrew","volume":"37","author":"Guggenheim","year":"1996","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yue, Y., Hsiao, Y.W., and Zhou, J.B. (2020). Association between MMP\/TIMP Levels in the Aqueous Humor and Plasma with Axial Lengths in Myopia Patients. Biomed Res. Int., 2020.","DOI":"10.1155\/2020\/2961742"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104265","DOI":"10.1016\/j.mvr.2021.104265","article-title":"Down-expression of the NLRP3 inflammasome delays the progression of diabetic retinopathy","volume":"139","author":"Ge","year":"2022","journal-title":"Microvasc. Res."},{"key":"ref_9","first-page":"703","article-title":"IL-18 promotes the secretion of matrix metalloproteinases in human periodontal ligament fibroblasts by activating NF-\u03baB signaling","volume":"19","author":"Wang","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1093\/intimm\/dxf108","article-title":"The role of IL-18 and IL-12 in the modulation of matrix metalloproteinases and their tissue inhibitors in monocytic cells","volume":"14","author":"Abraham","year":"2002","journal-title":"Int. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104949","DOI":"10.1016\/j.jprot.2023.104949","article-title":"Complement-mediated inflammation and mitochondrial energy metabolism in the proteomic profile of myopic human corneas","volume":"285","author":"Huang","year":"2023","journal-title":"J. Proteom."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"111822","DOI":"10.1016\/j.ejmech.2019.111822","article-title":"Development of small molecule inhibitors targeting NLRP3 inflammasome pathway for inflammatory diseases","volume":"185","author":"Zhang","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.redox.2015.01.008","article-title":"NLRP3 inflammasome: From a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases","volume":"4","author":"Abderrazak","year":"2015","journal-title":"Redox Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chen, Z., Xiao, K., and Long, Q. (2023). Up-Regulation of NLRP3 in the Sclera Correlates with Myopia Progression in a Form-Deprivation Myopia Mouse Model. Front. Biosci., 28.","DOI":"10.31083\/j.fbl2802027"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.cell.2012.03.036","article-title":"DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88","volume":"149","author":"Tarallo","year":"2012","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.imlet.2012.05.005","article-title":"Oxidative stress activates NLRP3 inflammasomes in ARPE-19 cells-implications for age-related macular degeneration (AMD)","volume":"147","author":"Kauppinen","year":"2012","journal-title":"Immunol. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s00109-015-1275-1","article-title":"Light induces NLRP3 inflammasome activation in retinal pigment epithelial cells via lipofuscin-mediated photooxidative damage","volume":"93","author":"Brandstetter","year":"2015","journal-title":"J. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exer.2014.05.001","article-title":"Reactive oxygen species activated NLRP3 inflammasomes prime environment-induced murine dry eye","volume":"125","author":"Zheng","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1016\/j.celrep.2015.05.023","article-title":"Iron toxicity in the retina requires Alu RNA and the NLRP3 inflammasome","volume":"11","author":"Gelfand","year":"2015","journal-title":"Cell Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s00109-019-01753-5","article-title":"Efficacy of novel selective NLRP3 inhibitors in human and murine retinal pigment epithelial cells","volume":"97","author":"Wang","year":"2019","journal-title":"J. Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6720","DOI":"10.1038\/s41598-018-25123-2","article-title":"Hsp90 inhibition as a means to inhibit activation of the NLRP3 inflammasome","volume":"8","author":"Piippo","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_22","unstructured":"Flurkey, K., Currer, J.M., and Harrison, D.E. (2007). The Mouse in Biomedical Research, Academic Press. [2nd ed.]."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.ophtha.2015.11.010","article-title":"Efficacy Comparison of 16 Interventions for Myopia Control in Children: A Network Meta-analysis","volume":"123","author":"Huang","year":"2016","journal-title":"Ophthalmology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/21\/15839\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:15:10Z","timestamp":1760130910000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/21\/15839"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,31]]},"references-count":23,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ijms242115839"],"URL":"https:\/\/doi.org\/10.3390\/ijms242115839","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,31]]}}}